POS1349 IMMUNOGLOBULIN G4-RELATED KIDNEY DISEASE’S PREDISPOSITION TO CHRONIC RENAL DYSFUNCTION, COMPLICATIONS OF MALIGNANCY, AND MORTALITY: A LONG-TERM NATIONWIDE MULTICENTER STUDY IN JAPAN
Authors: I. Mizushima, T. Saeki, D. Kobayashi, H. Hayashi, Y. Taniguchi, H. Nakata, S. Matsui, T. Nagasawa, M. Yanagita, M. Kawano
Journal: Annals of the Rheumatic Diseases (2022)

Background In immunoglobulin G4-related kidney disease (IgG4-RKD), persistent renal insufficiency may be observed despite the good initial response to glucocorticoids [1, 2] . However, its long-term prognosis in relation to renal function as well as malignancy and mortality has not been well clarified. Objectives To clarify the long-term renal prognosis, complications of malignancy, mortality, and factors related to those outcomes in IgG4-RKD. Methods We retrospectively reviewed the medical records of patients with IgG4-RKD diagnosed by the expert members of the IgG4-RKD working group in the Japanese Society of Nephrology. We investigated clinical, radiological, and histopathological features at baseline and course of renal function, complications of malignancy, and mortality during the long-term observation periods (median 71 months) in 75 patients. Using collected data, we calculated the crude incidence rates (IR) of chronic kidney disease (CKD) status, malignancy, and death. Cox regression analyses were performed to assess CKD-related factors. Additionally, we calculated the standardized incidence ratio (SIR) of malignancy and standardized mortality ratio (SMR) using national Japan statistics. Results Fifty-nine patients were male, and 16 were female (median age 70 years). At diagnosis, their median eGFR was 45.1 mL/min/1.73m 2 (interquartile range [IQR] 28.6-69.9). Seventy-two patients (96%) were treated with prednisolone at a median initial dose of 30 (IQR 30-39) mg/day, leading to a reasonable initial improvement of renal function. The IR of CKD was 30.2/100 person-years, and 66.7% (50/75) of the patients showed CKD at the last visit. Age- and sex-adjusted Cox regression analyses indicated that lower eGFR (per 10 mL/min/1.73m 2 , hazard ratio [HR] 0.70, 95% confidence interval [CI] 0.61-0.80), pre-existing hypertension (HR 2.39, 95% CI 1.32-4.34), and wider areas with inflammation (&gt;50% vs. &lt;10%, HR 2.55, 95% CI 1.07-6.08) or fibrosis (&gt;50% vs. &lt;5%, HR 2.84, 95% CI 1.18-6.85) in the biopsied renal specimens at treatment initiation had a significant impact on the time to CKD. Eight patients (10.7%) died during follow-up due to malignancy, severe infection, cerebral hemorrhage, or myocardial infarction. The crude mortality rate was 1.76/100 person-years, and a SMR calculated according to national Japan statistics was 0.97 (95% CI 0.42-1.90). On the other hand, 15 patients were diagnosed as having malignancies during follow-up. The IR of malignancy was 3.71/100 person-years, and the SIR of malignancy was 1.80 (95% CI 1.03-2.93). Conclusion This study suggests that pre-treated renal insufficiency and extensive renal inflammatory and fibrotic lesions are related to CKD under glucocorticoid therapy in IgG4-RKD. Similarly with the whole IgG4-related disease, IgG4-RKD may have an increased incidence of malignancy but a mortality rate equivalent to the age- and sex-matched Japanese population. References [1]Saeki T et al. The clinical course of patients with IgG4-related kidney disease. Kidney Int. 2013 Oct;84(4):826-33. [2]Mizushima I et al. Factors related to renal cortical atrophy development after glucocorticoid therapy in IgG4-related kidney disease: a retrospective multicenter study. Arthritis Res Ther. 2016 Nov 25;18(1):273. Disclosure of Interests None declared